Τρίτη 4 Ιουνίου 2019

Ethnopharmacology

Protective effect of Shaoyao Decoction against colorectal cancer via the Keap1–Nrf2–ARE signaling pathway

Publication date: 15 September 2019

Source: Journal of Ethnopharmacology, Volume 241

Author(s): Xiaoyan Wang, Shakir M. Saud, Xiwen Zhang, Weidong Li, Baojin Hua

Abstract
Ethnopharmacological relevance

Ulcerative colitis is one of the three high risk factors for colorectal cancer. Studies have found that about 20% of cancers are caused by repeated chronic inflammatory stimuli over a long period of time. Ulcer-related colorectal cancer is one of the main causes of death in patients with ulcerative colitis. At present, surgery is the first choice for the treatment of colorectal cancer, combined with radiotherapy and chemotherapy, which have serious side effects. However, reportedly, a compound prescription of Chinese traditional medicine Shaoyao Decoction (SYD) commonly used to treat damp-heat dysentery has anti-colorectal cancer effect. Thus this study described the effect of SYD to AOM/DSS-induced colon cancer model.

Aim of the study

In this study, modern biomedical approaches were employed for investigating the protective/preventive effects of SYD in mice with azoxymethane (AOM)/DSS-induced CRC.

Materials and methods

The mice pretreated with AOM/DSS were randomly allocated to SYDL, SYDM, SYDH group and SASP (sulfasalazine) group. Mice without AOM/DSS treatment were randomly divided into PBS control group and SYD control group.

Results

It was found that SYD inhibited the production of inflammatory cytokines, TNF-α, IL-1β, superoxide dismutase (SOD), and malonaldehyde (MDA), and increased the antioxidant indices, as measured by the mRNA expression of GRTRHO-1γ-GCScγ-GCSmNQO-1UGT1A1, and UGT1A10 in AOM-treated mice. Particularly, the expressions rates of NF-κB and Ki-67 in the SYD-treated experimental groups were significantly lower than those in the model group, indicating that the proliferative ability of the CRC tissues was weaker in the SYD-treated experimental groups. Moreover, the positive levels of Nrf2 in the SYD-treated experimental groups were slightly higher than those in the model group, suggesting that SYD exhibited antioxidant activity.

Conclusions

To sum up, our results suggest that SYD inhibits the development of acute/chronic colitis and prevents colitis-associated CRC by suppressing inflammation and preventing oxidative stress-induced cellular damage.

Graphical abstract

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Danhong Huayu Koufuye prevents venous thrombosis through antiinflammation via Sirtuin 1/NF-κB signaling pathway

Publication date: 15 September 2019

Source: Journal of Ethnopharmacology, Volume 241

Author(s): Han Liu, Peng Li, Juan Lin, Wenpei Chen, Haibiao Guo, Jianyun Lin, Jin Liu, Ziqi Lu, Xiaolan Yao, Yang Chen, Baoqin Lin

Abstract
Ethnopharmacological relevance

Danhong Huayu Koufuye (DHK), a compound traditional Chinese medicine, is composed of Salvia miltiorrhiza radix (Salvia miltiorrhiza Bge.), Angelicae Sinensis radix (Angelicae Sinensis (Oliv.) Diels.), Chuanxiongrhizoma (Ligusticum chuanxiong Hort.), Persicae semen (Prunus persica (L.) Batsch), Carthami flos (Carthamus tinctorius L.), Bupleuri radix (Bupleurum chinense DC.) and Aurantii fructus (Citrus aurantium L.). DHK prevents deep vein thrombosis (DVT) through antiinflammation. However, the antiinflammatory mechanism of DHK is still unknown.

Objective

The aim of this study was to evaluate whether DHK prevented venous thrombosis through antiinflammation via Sirtuin 1 (SIRT1)/NF-κB signaling pathway.

Methods

Inferior vena cava (IVC) stenosis-induced DVT rat model was established. Rats were administered with DHK (1.6, 3.2 or 6.4 mL/kg/d, p.o.), heparin (200 U/kg/d, i.v.), clopidogrel (25 mg/kg/d, p.o.), resveratrol (50 mg/kg/d, p.o.) or vehicle (p.o.) once daily for two days. Blood coagulation, blood fibrinolysis, blood viscosity, blood cell counts and platelet activity were evaluated. Serum levels of inflammatory cytokines were analyzed by enzyme-linked immunosorbent assay. Pathological changes were observed by hematoxylin-eosin (HE) staining. Protein expressions in thrombosed IVCs were evaluated by Western blot and/or immunofluorescence analyses. SIRT1 mRNA expression was analyzed by real-time quantitative polymerase chain reaction. Besides, SIRT1-specific inhibitor EX527 was pretreated to confirm the role of SIRT1/NF-κB signaling pathway in the antithrombotic effect of DHK.

Results

DHK remarkably prevented DVT. DHK had no effects on blood coagulation, blood fibrinolysis, blood viscosity, blood cell counts or platelet activity. But DHK significantly up-regulated protein and mRNA expressions of SIRT1, and reduced leukocytes infiltration into thrombus and vein wall, serum levels of inflammatory cytokines, and protein expressions of acetylated p65 (Ace-p65), phosphorylated p65 (p-p65) and tissue factor (TF). Moreover, the antithrombotic effect of DHK was significantly abolished by EX527.

Conclusion

DHK may prevent DVT by inhibiting inflammation via SIRT1/NF-κB signaling pathway.

Graphical abstract

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Preparation, structural identification and intervention on immunodeficiency mice of enzymatic peptides from Mauremys mutica and Cuora trifasciata

Publication date: 15 September 2019

Source: Journal of Ethnopharmacology, Volume 241

Author(s): Yan-bo Lv, Qing Zhou, Yang Fan, Jiu-liang Zhang

Abstract
Ethnopharmacology relevancy

Mauremys mutica (Asian yellow pond turtle, YPT) and Cuora trifasciata (Chinese three-striped box turtle, TBT) are traditional Chinese medicine. They possess many biological characteristics, such as immune enhancement, anti-inflammatory, anti-cancer effects. They have long been used as folk anti-cancer drugs in central and southern China. However, there was no studies to compare the immune enhancement effect of YPT and TBT, nor to identify the structures of YPT peptides and TBT peptides.

Aims of the study: The aim of this study was to evaluate the protective efficacy of YPT and TBT on immunodeficient mice and to compare the primary structures of YPT peptides and TBT peptides.

Materials and methods

The protein extracts were extracted using boiling water, and peptides were obtained by hydrolyzing protein extract with alkaline protease. Cyclophosphamide (CTX) was used to induce immunodeficiency in mice. The immune enhancement effect was evaluated by measuring body weight gain curve, thymus index, spleen index, serum SOD activity and GSH-Px activity. Primary structure of peptides identified by HPLC-ESI-MS/MS.

Results

The protein extracts and peptides of the YPT and TBT had certain recovery effects on immunodeficient mice. YPT peptides has the best effect on the recovery of damaged immune organs in mice. In the identification of the primary structure of the polypeptide, YPT and TBT have some similar peptide segments, but there are also many differences. This may be the reason why they have the same function and different effects, which lays the foundation for the follow-up mechanism researches.

Conclusions

Two kinds of healthy turtle protein extracts and peptides had certain recovery effects on immune injury in mice. YPT peptides possessed the best effect on the recovery of immunodeficiency.

Graphical abstract

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Integrated pathological cell fishing and network pharmacology approach to investigate main active components of Er-Xian decotion for treating osteoporosis

Publication date: 15 September 2019

Source: Journal of Ethnopharmacology, Volume 241

Author(s): Nani Wang, Pingcui Xu, Xuping Wang, Weixuan Yao, Zhongming Yu, Renjie Wu, Xiaowen Huang, Yuyang Si, Dan Shou

Abstract
Ethnopharmacological relevance

Oxidative damage to osteoblasts was a key factor in the development of osteoporosis. Er-Xian Decotion (EXD) is widely used in China for the treatment of osteoporosis, which has a variety of antioxidant active ingredients. EXD may be an important source of protection against oxidative damage in osteoblasts, but the anti-osteoporotic active components of EXD is currently unclear.

Aim of the study

This work established an effective and reliable drug screening method to find main active ingredients in EXD (M-EXD) that can protect osteoblasts against oxidative stress and achieve anti-osteoporosis effects.

Materials and methods

H2O2-induced osteoblast cell fishing with UHPLC-QTOF/MS was firstly used to discover the potential active components from EXD. Afterword, the EXD compound-osteoporosis target network was constructed using network pharmacology, thus potentially anti-osteoporosis ingredients were founded, and their combination were defined as the M-EXD. Finally, pharmacology effects of M-EXD was evaluated by ovariectomized rats, prednisolone induced-zebrafish and H2O2-induced osteoblasts.

Results

40 candidate active ingredients in EXD were initially screened out via pathological cell fishing. According to network pharmacology result, M-EXD consisted of 13 ingredients since they had a close relationship with 65 osteoporosis-related targets. Pharmacological evaluation showed that M-EXD significantly ameliorated oxidative stress in H2O2-induced osteoblast model, evidently reversed the activity of ALP, ROS, GSH-px, NO and MDA compared with the model group. M-EXD showed better anti-oxidative activities than individual ingredients, presenting obvious synergetic effects. In osteoporosis rat and zebrafish models, M-EXD also demonstrated good anti-osteoporotic properties by mitigating the osteoporosis bone loss and increasing serum bone morphogenetic protein 2, and reversing osteocalcin expression in bone tissue. It significantly ameliorated oxidative stress in the in-vivo models. Moreover, M-EXD and EXD showed similar anti-osteoporotic and anti-oxidative properties, while the rest components of EXD had no satisfactory anti-osteoporotic efficacy.

Conclusions

Our work successfully identified the main active components in EXD, which could represent the efficacy of EXD on treating osteoporosis, and meanwhile, it also provided an effective strategy to investigate active ingredients from natural medicines, which might be helpful for drug development and application.

Graphical abstract

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Ethnopharmacology in the Upper Guadiana River area (Castile-La Mancha, Spain)

Publication date: 15 September 2019

Source: Journal of Ethnopharmacology, Volume 241

Author(s): Diego Rivera, Alonso Verde, José Fajardo, Concepción Obón, Vicente Consuegra, José García-Botía, Segundo Ríos, Francisco Alcaraz, Arturo Valdés, Alejandro del Moral, Emilio Laguna

Abstract
Ethnopharmacological relevance

Determining traditional remedies for human pathologies is relevant, when compared with the standard materia medica of the pharmacopoeias and dietary supplement databases, because we can assess the species and uses that have been previously studied and target understudied species for further pharmacological investigation.

Background

The aim of this study was to systematically record and analyze medicinal uses of natural resources (Plantae, Animalia, Fungi and minerals), mostly local, in the territories adjoining the upper Guadiana River and its tributaries.

We were particularly interested in recording resources and pathologies linked to wetland areas, especially in the National Parks Las Tablas de Daimiel and Cabañeros. Wetlands are interesting because they present a double face in relation with human health: Wetlands furnish hydration, safe water, nutrition, and medicinal resources; are places from which people derive their livelihood. However wetlands are also sites of exposure to pollution or toxicants, and infectious diseases; and sites of physical hazards.

We wanted to identify procedures for preparation of medicinal formulae and routes of administration. We also intended to detect whether a geographical pattern exists or not in our records in relation to the use of local resources.

Methods

We used semi-structured interviews with one-to-one informants or groups, from 1998 to 2018. Raw data were introduced in a Firebird database and analyzed. To identify ingredients and pathologies we consulted local floras and epidemiological literature. Finally, we compared documented pathologies, remedies and ingredients in the historical context of medicinal uses of natural resources in Castile-La Mancha and especially in Ciudad Real.

Results

126 pathologies and 220 species furnishing ingredients have been recorded from the interviews. In total, 188 are plants and 20 animals. The most commonly used species include Malva sylvestris, Phlomis lychnitis, Genista tridentata and Thymus mastichina. Most records refer to flowers, or fruits, of locally available plant species, classified as Mediterranean, European or widespread that belong to the Lamiaceae, Compositae or Leguminosae. Ingredients which are collected in open shrublands, known as "garrigue", and dry grasslands furnish a relevant proportion of records while the imported ingredients remain marginal. The contribution of wetlands, riverine habitats and irrigated fields and gardens as a source of medicinal resources is 36% of the records. It is relatively high considering its limited presence in terms of total extension within the study area. The most frequently reported diseases are respiratory, gastrointestinal, dermatological and infectious or parasitic.

Conclusions

Along the Guadiana River in the Ciudad Real province exists a wide and deep knowledge of traditional remedies for the treatment of common pathologies, based fundamentally on the use of local flora, fauna and mineral resources. The uses and ingredients documented are useful for further pharmacological investigation to improve health care for a wide range of pathologies.

Graphical abstract

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Carica papaya seed extract slows human sperm

Publication date: 15 September 2019

Source: Journal of Ethnopharmacology, Volume 241

Author(s): V. Ghaffarilaleh, D. Fisher, R. Henkel

Abstract
Ethnopharmacological relevance

Traditional healers use Carica papaya seeds as a remedy for diseases and as a contraceptive for men and abortion in women.

Material and methods

Semen samples from 35 healthy men were allowed to liquefy and subsequently incubated for 60 min in Human Tubular Fluid medium containing 1% bovine serum albumin with aqueous C. papaya seed extract at concentrations of zero, 0.025, 0.25, 2.5, 25, 250 and 2500 μg/ml. Afterwards, sperm were washed and used for assessment of capacitation and acrosome reaction, DNA fragmentation, vitality, motility, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP).

Results

The extract showed no effects on straight-line velocity, linearity, straightness, beat-cross frequency and the percentage of capacitated, acrosome-reacted sperm. In contrast, vitality, total motility, progressive motility, curvilinear velocity, average-path velocity and the percentages of hyper-activated, ROS-positive and MMP-intact sperm decreased significantly (P < 0.05), while the percentage of DNA-fragmented sperm increased (P < 0.05).

Conclusions

Our data show that aqueous C. papaya seed extract significantly and negatively affects sperm motility parameters crucial for fertility; and thus, poses as a likely candidate for male contraception.

Graphical abstract

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Mass spectrometry-based urinary metabolomics for the investigation on the mechanism of action of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves against ischemic stroke in rats

Publication date: 15 September 2019

Source: Journal of Ethnopharmacology, Volume 241

Author(s): Rongjin Wang, Liqiang Shi, Shu Liu, Zhiqiang Liu, Fengrui Song, Zhiheng Sun, Zhongying Liu

Abstract
Ethnopharmacological relevance

As a traditional Chinese medicine, Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves (ESL) can treat ischemic, neurasthenia, and hypertension diseases. However, only few studies have been conducted on the mechanism of action of ESL for ischemic disease treatment.

Aim of the study

This study aimed to discover the potential biomarkers in the rats caused by ischemic stroke and build a gene–enzyme–biomarker network to explore the mechanism of ESL treatment on ischemic stroke further.

Materials and methods

The urinary metabolomics strategy was developed by combining UPLC-Q-TOF/MS with multivariate data analysis. The gene-enzyme-biomarker network was built by Cytoscape 3.6.0 on the basis of the potential biomarkers filtered out via urinary metabolomic analysis. Then, the potential target enzymes of ESL in the treatment of ischemic stroke were selected for further validation analysis via the ELISA kits.

Results

A total of 42 biomarkers associated with ischemic stroke have been identified, among which 38 species can be adjusted by ESL, including 5′-methylthioadenosine, prostaglandin A2, l-methionine, aldosterone, 11b-hydroxyprogesterone, prostaglandin E3, dehydroepiandrosterone, taurine, 5-methoxyindoleacetate, and p-cresol glucuronide. These biomarkers were involved in several metabolic pathways, including taurine and hypotaurine, arachidonic acid, cysteine and methionine, steroid hormone biosynthesis, tryptophan, and tyrosine metabolism pathways. The gene–enzyme–biomarker network was built, and three predicted target proteins, including cyclooxygenase-2 (COX-2), monoamine oxidase (MAO), and nitric oxide synthase (NOS), were selected as the potential target enzymes for ESL in ischemic stroke treatment.

Conclusions

All results showed that ESL can play a therapeutic role in treating ischemic stroke through different pathways. This study will provide an overall view of the mechanism underlying the action of ESL against ischemic stroke.

Graphical abstract

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Bioactivities of serotonin transporter mediate antidepressant effects of Acorus tatarinowii Schott

Publication date: 15 September 2019

Source: Journal of Ethnopharmacology, Volume 241

Author(s): Feng-Hong Zhang, Zhi-Mei Wang, Yan-Ting Liu, Ji-Sheng Huang, Shuang Liang, Hong-Hua Wu, Yan-Tong Xu

Abstract
Ethnopharmacological relevance

Acrorus tatarinowii Schott has been widely used in the treatments of neuropsychiatric and digestive disorders in clinical practices of traditional Chinese medicine for thousands of years. Both clinical and preclinical studies demonstrated antidepressant effects of A. tatarinowii. However, the possible action mechanisms of antidepressant effects of A. tatarinowii remain unraveled.

Aim of the study: The present study aimed to investigate the roles of serotonin transporter (SERT) in antidepressant effects of A. tatarinowii.

Materials and methods

Antidepressant effects of water extract of A. tatarinowii were evaluated by forced swimming test (FST), tail suspension test (TST) and locomotor activity test. The water extract was analyzed by ultra high performance liquid chromatography (UPLC) method. Two major fractions of A. tatarinowii, petroleum ether extract and water extract after petroleum ether processed, were prepared and analyzed by UPLC method. Further, volatile oil extracted by ether extraction, solid phase micro-extraction (SPME) and hydro-distillation were compared and analyzed by gas chromatography-mass spectrometer (GC-MS) method. Finally, major constituents of water extract of A. tatarinowii were isolated by preparative high performance liquid chromatography (HPLC) and identified by extensive spectroscopic analyses. Effects of all of the above mentioned samples on SERT activity were tested by a high content assay (HCA).

Results

Results of FST, TST and locomotor activity confirmed that water extract of A. tatarinowii significantly decreased mice immobility time but did not change mice locomotor activity. UPLC analysis results revealed that the water extract contained trace amount of β-asarone (0.0004206%) and α-asarone (0.0001918%). HCA results demonstrated that the water extract significantly enhanced SERT activity at 100 μg/mL. Further, GC-MS and UPLC analyses revealed that petroleum ether extract contained high content of β-asarone (45.63%) and α-asarone (12.50%). GC-MS analysis results demonstrated that the volatile oil extracted by ether extraction, SPME and hydro-distillation contained similar major components. HCA results verified that the petroleum ether extract significantly enhanced SERT activity at 1.56 μg/mL. Moreover, UPLC analysis of water extract after petroleum ether processed did not show any characteristic peaks. HCA results demonstrated that this extract significantly inhibited SERT activity at 50–100 μg/mL. Finally, phytochemistry investigation on the water extract of A. tatarinowii afforded seven constituents including veratric acid (9), anisic acid (7), 3,4,5-trimethoxybenzoic acid (3), trans-isoferulic acid (2), 2,4,5-trimethoxybenzoic acid (11), 4-hydroxybenzoic acid (6) and syringic acid (13). Their structures were established on the basis of nuclear magnetic resonance (NMR) and mass spectrometer (MS) data and comparative UPLC analyses. HCA results demonstrated the major components of the water extract of A. tatarinowii demonstrated SERT enhancement/inhibition activities.

Conclusions

This study first systematically demonstrated the roles of SERT activity in antidepressant effects of A. tatarinowii, including water extract, major fractions and main constituents. These results revealed that A. tatarinowii could regulate SERT activities in bidirectional ways.

Graphical abstract

Serotonin transporters play important roles in antidepressant effects of Acorus tatarinowii.

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Alkaloids of dendrobium nobile lindl. Altered hepatic lipid homeostasis via regulation of bile acids

Publication date: 15 September 2019

Source: Journal of Ethnopharmacology, Volume 241

Author(s): Si Huang, Qing Wu, Hao Liu, Hua Ling, Yuqi He, Changhong Wang, Zhengtao Wang, Yanliu Lu, Yuanfu Lu

Abstract
Ethnopharmacological relevance

Accumulation of hepatic lipid promotes systemic metabolic dysfunction and results in fatty liver. Our previous studies have shown that the alkaloids of Dendrobium nobile Lindl. (DNLA) could regulate the lipid metabolism gene expression in livers of mice. However, the protective effects on hepatic lipid homeostasis and the underlying mechanisms are still unclear.

Materials and methods

The C57BL/6 male mice were randomly divided into four groups, including control group, model group, DNLA treatment group, and simvastatin positive control group. Mice in the control group and the other three groups were fed with control diet and high fat diet during the full course of this study, respectively. Hepatic lipid accumulation was induced by HFD in mice after 18 weeks of feeding. DNLA (15 mg/kg) and simvastatin (20 mg/kg) were administrated intragastrically in the DNLA treatment group and simvastatin positive control group for another 18 weeks, respectively. HE staining and Oil-Red-O staining of liver tissues were observed. TC and TG levels in liver were assayed. The amount of major bile acids in mice livers were quantified by UPLC-MS. Expression levels of genes were tested by the real-time PCR.

Results

The results of HE staining and Oil-Red-O staining showed that DNLA could improve hepatic lipid homeostasis. DNLA significantly decreased liver TC and TG levels in the DNLA group. Moreover, the UPLC-MS analysis showed that DNLA did not only influence the hepatic bile acid quantity but did raise the hydrophilicity. Compared with the model group, DNLA decreased the hepatic levels of several free bile acids, including LCA, DCA, CA, and CDCA, and increased most important taurine-conjugated bile acids levels in liver, including TMCAs, TCDCA, TUDCA, and THDCA. In addition, DNLA also decreased the CA/CDCA ratio. The gene expression levels of Cyp27a1Cyp3a11Fxr, and Shp were up-regulated in DNLA treatment group.

Conclusion

DNLA may improve the hepatic abnormal lipid profile of HFD-fed mice via two pathways: (1) enhancing the taurine-conjugated bile acids which are highly hydrophilic and contribute to the excretion of cholesterol; (2) decreasing the CA/CDCA ratio which is positively related to cholesterol absorption.

Graphical abstract

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Dalspinin isolated from Spermacoce hispida (Linn.) protects H9c2 cardiomyocytes from hypoxic injury by modulating oxidative stress and apoptosis

Publication date: 15 September 2019

Source: Journal of Ethnopharmacology, Volume 241

Author(s): R. Lakshmi Sundaram, Hannah R. Vasanthi

Abstract
Ethnopharmacological relevance

Spermacoce hispida (S.hispida), a potential medicinal plant has been traditionally used as an antibacterial, antieczemic, antihypertensive, antidiabetic and antihyperlipidemic agent. Although, this plant has been claimed to protect against oxidative injury and inflammatory conditions in recent studies, its cardioprotective effect and the active constituents responsible for its bioactivity is sparsely studied. Hence this work is undertaken to study the active biomolecule responsible for modulating the cardiomyocytes on hypoxic injury relevant to its ethanopharmacology.

Aim of the study

The current study is to isolate and characterize a bioactive molecule from S.hispida, which exhibits protection against hypoxic injury in an in vitro hypoxic model of cultured H9c2 cardiomyocytes.

Materials and methods

The methanolic extract of S.hispida plant was fractionated with various solvents sequentially. The ethyl acetate fraction that was concentrated and chromatographed over silica gel column eluted 18 fractions, which yielded 5 compounds, which were characterized using spectral data. The isolated new compound was further tested for its protective effect against hypoxic injury, wherein cobalt chloride (CoCl2) was used to induce hypoxia in H9c2 cardiomyoblasts. To evaluate the protective effect of the isolated compound, the markers of oxidative stress, apoptosis, and cell death were checked by endogenous levels of antioxidants, [malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH)], lactate dehydrogenase (LDH) activity and immunoblot (HIF-α, Bcl2, Bax, procaspase and cleaved caspase-3).

Results

Among the five compounds isolated and characterized from S. hispida methanolic extract, β-sitosterol, ursolic acid, quercetin and rutin were known phytochemicals, while the new isoflavone was identified as dalspinin-7-0-β-D-galactopyranoside (DBG).

Among the isolated compounds, the antioxidant potential of DBG confirmed by DPPH free radical scavenging and ORAC assays was superior. CoCl2-induced hypoxic condition significantly decreased cell viability, SOD activity, GSH concentration and increased the level of MDA and LDH activity. Western blot studies revealed an upregulation of HIF-1α, Bax and caspase and down regulation of Bcl-2 expression. The oxidative abnormalities were ameliorated by DBG pretreatment, as deduced by the reduced CoCl2-induced cytotoxicity, MDA concentration, LDH activity and the expression of HIF-1α, Bax and caspase and the enhanced levels of SOD, GSH and Bcl2 expression in a dose-dependent manner.

Conclusion

DBG protects H9c2 cells from CoCl2-induced hypoxic damage by mitigating oxidative stress and preserving cell viability. The overall findings highlight the protective action of DBG, a potential source of antioxidant of natural origin against hypoxic injury and may help in mitigating the progress of oxidative stress in cardiac cell death.

Graphical abstract

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Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Health Sciences and Biomedical Research

Pediatric renal transplants
RB Nerli, Shridhar C Ghagane

Indian Journal of Health Sciences and Biomedical Research (KLEU) 2019 12(2):99-100



Burnout among healthcare professionals: Is it a cause for concern?
Punnya V Angadi

Indian Journal of Health Sciences and Biomedical Research (KLEU) 2019 12(2):101-102



Maternal mental health and its influence on infant growth and development: A systematic review of observational studies in South and East Asia
Shubhashree Venkatesh, J Vindhya, Anita Nath

Indian Journal of Health Sciences and Biomedical Research (KLEU) 2019 12(2):103-111

Maternal mental stress during pregnancy is an important public health concern. There is strong evidence from the Western world to support the presence of a significant association between maternal stress in pregnancy and adverse outcomes in the offspring. There are fewer studies from the South and East regions of Asia. The search was conducted according to the PRISMA criteria. Databases which included NCBI PubMed, Scopus, and Embase were used to search for relevant studies according to the eligibility criteria. Most of the studies have shown a significant relation between stress, depression, and anxiety during various stages of pregnancy with delayed mental, motor, and behavioral development of the child. Although studies from the region show a significant relation between various stress factors during pregnancy and child development, more such studies are needed, especially those using potential biomarkers as indicators of pregnancy-related stress. 


Cytotoxic activity of endophytes isolated from Allamanda blanchetii A. DC
Harsha D Pednekar, Harsha V Hegde, Pramod J Hurakadale, Jyoti D Wagawade, Kishore G Bhat, Chetana Bogar

Indian Journal of Health Sciences and Biomedical Research (KLEU) 2019 12(2):112-116

AIM: To evaluate the cytotoxic potential of endophytic fungi isolated from A. blanchetii. MATERIALS AND METHODS: Endophytic fungi were isolated from A. blanchetii using surface sterilization methods, grown in different types of media to ascertain their suitability for growth. Mass culture was prepared using suitable media and extracts using several solvents were prepared and dried. These extracts were later evaluated using MTT assay for their cytotoxic potential. RESULTS: Hydroalcoholic extract of Phomopsis species exhibited better cytotoxicity (80 &#956;g/ml) when compared ethyl acetate extract of the same 160 &#956;g/ml. Similarly, ethyl acetate extract of Phomopsis species, ethyl acetate extract of Alternaria aff. raphani J. W. Groves and Skolko also demonstrated cytotoxicity of 160 &#956;g/ml in MTT assay against MCF 7 cell line. CONCLUSION: Both the species of Phomopsis and Alternaria have shown significant cytotoxicity in MTT assay. 


Impact of refractive error correction on mental and visual development in children with global developmental delay
KS Smitha, VD Patil, Mahesh D Kamate, Madhav Prabhu, Umesh Harakuni, OP Rakshitha

Indian Journal of Health Sciences and Biomedical Research (KLEU) 2019 12(2):117-122

PURPOSE: The purpose of the present study is to evaluate visual acuity and refractive status in children with global developmental delay (GDD) and to study the effect of early correction of refractive errors on vision and developmental quotient (DQ). METHODS: In this case series data with pre&#8211;post design, 100 consecutive children from 1 to 5 years of age diagnosed with GDD attending the child development clinic and referred to ophthalmology were evaluated for ocular complaints, status of visual acuity, and type of refractive error. Glasses were prescribed on the basis of cycloplegic retinoscopy. Etiological diagnosis and DQ were documented. Follow-up was done after 6 months for visual acuity, DQ, and qualitative questionnaire administered for the caretaker. Statistical analysis was done using the Chi-square test. RESULTS: Fifty-six children were &#60;2.5 years of age and 44 children were &#62;2.5 years. Severe GDD prevalence was more in children &#60;2.5 years (43&#37;) and mild GDD in &#62;2.5 (50&#37;). Of 47 who showed improvement in vision, 39 (71&#37;) showed improvement in social behavior also, which was statistically significant. In children &#60;2.5 years, more improvement in DQ was seen in the moderate intellectual disability group after refractive error correction. However, in the children of 2.5 years and above, more improvement was seen in the severe group. Overall, improvement in DQ in children from 1 to 5 years was statistically significant at 14&#37;. CONCLUSION: Harmful effects of sensory visual deprivation on the development and functioning can be dampened by a simple and cost-effective approach of spectacles therapy which makes a spectacular effect in the case of children with GDD. 


Quantification of mast cells in reactive oral lesions – A clue to the morphologic diversity
Saurabh Shekar, Punnya V Angadi

Indian Journal of Health Sciences and Biomedical Research (KLEU) 2019 12(2):123-126

OBJECTIVE: Inflammatory fibrous hyperplasia (IFH), pyogenic granuloma (PG), peripheral ossifying fibroma (POF), and peripheral giant cell granuloma (PGCG) are common oral soft-tissue reactive lesions that correspond to excessive connective tissue proliferation as a reaction to trauma or irritational factors local to the oral cavity. These lesions have specific differences in their histopathologic appearances and behavior in spite of having common etiologic factors. Mast cells (MCs) are immune-regulatory cells that have an important role to play in oral inflammation and have also been associated with tissue remodeling and fibrosis in various disorders. METHODOLOGY: MCs were stained with toluidine blue in cases of IFH (20), PG (20), PGCG (20), and POF (20) along with normal gingiva tissue as control (5) for quantification and comparison among them. RESULTS: The mast cell count was low in normal mucosa but a progressive increase was seen from PGCG to IFH to POF with maximum mast cells were evident in PG. There was a significant difference noted in the MC counts between the normal mucosa and the oral reactive lesions (P &#60; 0.05). However, the difference in the MC count did not reach statistical significance among the reactive lesions (P &#61; 0.400). CONCLUSION: MCs emerged as significant players in the pathogenesis and histopathologic diversity of oral reactive lesions by their effects on fibroblasts and endothelial cells. 


Knowledge and perceptions of mothers of under-five children attending a tertiary care hospital about childhood diarrhea: A cross-sectional study
Dipak Kumar Dhar, Nilratan Majumder

Indian Journal of Health Sciences and Biomedical Research (KLEU) 2019 12(2):127-131

CONTEXT: Diarrhea is a major cause of morbidity and mortality among young children. The incidence of diarrhea has remained almost unchanged over the years, highlighting the scope of prevention. A mother is the primary caregiver of a child. Her perceptions and knowledge of a disease determine her care-seeking behavior and health of the child by extension. AIM: The aim of the present study was to assess the level of knowledge of mothers about different aspects of childhood diarrhea. SETTINGS AND DESIGN: A hospital-based, descriptive cross-sectional study was carried out in the Department of Paediatrics, Agartala Government Medical College and G. B. Pant Hospital, Agartala, Tripura, over a period of 2 months. MATERIALS AND METHODS: The sample size for the study was 700. Convenience sampling technique was used to interview 700 mothers of under-five children, using a predesigned structured interview format. STATISTICAL ANALYSIS USED: Data were analyzed using SPSS version 13. Descriptive statistics and Chi-square test were used for analysis. P &#60; 0.05 was considered as statistically significant. RESULTS: Majority of the mothers had a correct perception of the symptoms and causes of diarrhea. Most of them also knew about the importance of handwashing and had also heard about oral rehydration solution (ORS). However, their awareness about the warning signs indicating severe dehydration and the role of ORS in diarrhea was very poor. Educational level was found to be significantly associated with the knowledge. CONCLUSIONS: To bring down the mortality rate, mothers have to be made aware of the warning signs and the role of ORS because adequate knowledge is a critical component of the decision-making process. 


Prevalence of Vitamin D deficiency in patients with acute exacerbations of bronchial asthma: A one-year hospital-based cross-sectional study
Srinija Kummaraganti, Gajanan S Gaude

Indian Journal of Health Sciences and Biomedical Research (KLEU) 2019 12(2):132-138

BACKGROUND AND OBJECTIVES: Bronchial asthma is one of the most common chronic diseases. In India, bronchial asthma has 66&#37; frequency of reported exacerbations. Vitamin D has action on pro-inflammatory mediators and smooth muscle function and proliferation, which has a direct relevance for lung function in asthma. This study was done to investigate the prevalence of Vitamin D deficiency in patients presenting with asthma exacerbations and to assess the correlation between decreased levels and various indicators of severity of exacerbations. MATERIALS AND METHODS: A total of 118 participants of whom 93 patients had acute exacerbations of bronchial asthma were included in this study. Vitamin D levels were analyzed among different subgroups based on asthma control, severity, and severity of exacerbations. Vitamin D levels were correlated to forced expiratory volume in 1 s (FEV1)&#37; predicted, body mass index (BMI), steroid use, and number of exacerbations in the previous 1 year. RESULTS: Prevalence of Vitamin D deficiency was 88.2&#37;. Mean Vitamin D (&#177; standard deviation [SD]) level was 12.50 &#177; 6.41 ng/ml, which was lower than that of patients in remissions (30.61 &#177; 4.00 ng/ml). Mean FEV1&#37; predicted (&#177;SD) was 54.06&#37; &#177;15.39&#37;. Patients with severe asthma and uncontrolled asthma had the lowest Vitamin D levels compared to the other subgroups (P &#60; 0.0001). Vitamin D levels were lower in patients with severe exacerbation (8.61 &#177; 4.16 ng/ml) as compared to mild-moderate exacerbation (17.44 &#177; 5.25 ng/ml). Vitamin D levels were positively correlated with FEV1&#37; predicted (r &#61; 0.66) and were negatively correlated with BMI (r &#61; &#8722;0.89), steroid usage (r &#61; &#8722;0.85), and the number of exacerbations in the previous 1 year (r &#61; &#8722;0.83). All were statistically significant (P &#60; 0.05). CONCLUSION: Vitamin D deficiency is highly prevalent in patients during exacerbations of bronchial asthma. It is also associated with lower lung functions and increased number of exacerbations. Thus, improving Vitamin D status might be effective in the prevention and treatment of bronchial asthma and exacerbations. 


Prescribing patterns of Virechana Karma in terms of Shuddhi Lakshana
Shawan Barik, Buduru Sreenivasa Prasad

Indian Journal of Health Sciences and Biomedical Research (KLEU) 2019 12(2):139-153

BACKGROUND: The widespread use of various drugs in a single procedure and the increasing recognition of Shuddhi achieved as per the classics to provide the best result have stimulated interest in the manner in which physicians prescribe drugs. The main sources of this information can be found at the institutional-level like hospitals. These sources reveal a varied prescribing patterns in terms of drugs used for Snehapana, drugs used for Sarvanga abhyanga, and also in terms of drug selection for Virechana karma. It also reveals the pattern in the selection of dose and the duration of the treatment vary greatly among physicians according to their place, practice, disease, and the condition of the patient. METHODS: Therefore, a prospective study was conducted from May 2016 to December 2017 at KAHER&#39;s Shri BMK Ayurveda Hospital and Research Centre, Belagavi, Karnataka, India. A total of 1138 individuals were screened among which 319 individuals were taken as per the inclusion criteria, in which 300 participants completed the study. RESULTS: The outcome was measured on the basis of SamyakShuddhi Lakshana (SSL) of Snehana and Virechana karma. The study revealed that 51.33&#37; of the individuals achieved avaraShuddhi, 42.33&#37; achieved MadhyamaShuddhi, and 6.34&#37; achieved PravaraShuddhi. In mridu koshtha, a total of 160&#8211;200 ml of ghrita intake can attain 10&#8211;11 vegas, in Madhyama koshtha total of 295&#8211;1130 ml of ghrita intake can attain 13&#8211;18 vegas, and in krurukoshtha total of 90&#8211;520 ml of ghrita intake can attain up to 21 vegas over a period of 3 or 5 days. 92.67&#37; times Trivritleha was observed as prescribed drug which also has 30 min onset of Virechanavega with proper snehaSamyakShuddhi. DISCUSSION AND CONCLUSION: The study is the precursor to improve prescribing patterns and quality of care and thus provides a population based approach to advance clinical pharmacology and improved health outcomes resulting from improved prescribing choices. 


A community-based cross-sectional study about knowledge, attitude, and practices of food safety measures among urban households
Shilpa Reddy Ganta, Deepti M Kadeangadi

Indian Journal of Health Sciences and Biomedical Research (KLEU) 2019 12(2):154-159

OBJECTIVE: The objective of this study was to assess knowledge, attitude, and practices of food safety measures among urban households of Belagavi using the World Health Organization (WHO) &#8220;Five keys for food safety.&#8221; MATERIALS AND METHODOLOGY: A community-based cross-sectional study was conducted from January 1, 2017, to December 31, 2017 among 400 women aged above 18 years who were involved in food preparation at urban households in the field practice area of Ashok Nagar, Belagavi, Karnataka, India. Data were collected using pretested and predesigned questionnaire based on the WHO five keys for food safety. Households were selected based on systematic random sampling. Statistical analysis was done by percentages, mean and standard deviation, and ANOVA using IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Cor. RESULTS: The mean age of the participants was 37.96 &#177; 14.9 years, and the mean scores of knowledge, attitude, and practice regarding food safety were 7.1 &#177; 1.47 out of total score of 11, 15.45 &#177; 1.65 out of total score of 18, and 30.18 &#177; 4.21 out of total score of 40, respectively. The mean knowledge score was found to be lower in the age group of &#62;35 years (P &#60; 0.05, F &#61; 5.7415) and socioeconomic status Classes III, IV, and V (P &#60; 0.05, F &#61; 1.828), and these differences were found to be statistically significant. CONCLUSION: Knowledge and attitude scores regarding food safety were good, but food safety practice scores were lower. Among the WHO five keys for food safety, knowledge, attitude, and practices regarding &#8220;cook thoroughly&#8221; and &#8220;keep food at safe temperature&#8221; were observed to be lower. 


Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Tzu Chi Medical Journal, a publication of Buddhist Compassion Relief Tzu Chi Foundation

Therapeutic potential of intravesical injections of platelet-rich plasma in the treatment of lower urinary tract disorders due to regenerative deficiency
Qian-Sheng Ke, Jia-Fong Jhang, Teng-Yi Lin, Han-Chen Ho, Yuan-Hong Jiang, Yuan-Hsiang Hsu, Hann-Chorng Kuo

Tzu Chi Medical Journal 2019 31(3):135-143

The bladder urothelium plays an important role of barrier function to prevent influx of urinary toxic substance and bacteria. When there is insult to the urinary bladder, the urothelium will start to regenerate on injury. However, several factors might affect the regenerative function of bladder urothelium, including aging, chronic inflammation, and system diseases such as diabetes and chronic kidney diseases (CKDs). Impairment of bladder mucosal regenerative function might result in defective urothelial cell differentiation as well as barrier function, which might be the underlying pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) and recurrent bacterial cystitis. Our previous immunohistochemistry (IHC) study and electron microscopic study revealed that the loss of normal umbrella cells and defective junction proteins in IC/BPS and recurrent cystitis. Platelet-rich plasma (PRP) has been previously used in many medical aspects as regenerative medicine therapy. PRP is rich in many growth factors and cytokines which modulate the process of inflammation and regeneration in the wound healing process. Recent pilot studies have shown that intravesical PRP injections improve IC symptoms and yield a success rate of 70&#37; at 3 months after treatment. The results highly suggest that PRP injection could improve urothelial regenerative function and reduce chronic inflammation in IC patients. This article reviews recently published researches on the urothelial dysfunction biomarkers, urothelial cell differentiation, and urinary regenerative and inflammatory proteins in patients with IC/BPS or recurrent bacterial cystitis. The pathophysiology of the insufficient urothelial regeneration and differentiation; and chronic inflammation may induce urothelial dysfunction and further affect the regenerative ability of the diseased bladder urothelium in IC/BPS and recurrent bacterial cystitis are discussed. 


Anticoagulants for cancer-associated ischemic stroke
Jin-Yi Hsu, An-Bang Liu

Tzu Chi Medical Journal 2019 31(3):144-148

Patients with cancer-associated ischemic stroke pose similar clinical manifestations and image characteristics, mainly embolic infarction, as patients with atrial fibrillation do. D-dimer, a degraded product of fibrin polymer, is a useful indicator of hypercoagulability, which frequently increases in cancer-associated stroke, but not in stroke resulted from atrial fibrillation. The level of serum D-dimer is associated with mortality, prognosis, and recurrence of systemic thromboembolism in these patients. Theoretically, drugs block coagulation cascade, such as heparin and low-molecular-weight-heparin (LMWH), oral direct anticoagulants, could attenuate the status of hypercoagulation and decrease the amount of D-dimer. These drugs may be helpful to prevent thromboembolic events in patients with cancer-associated hypercoagulability. Vitamin K antagonist, warfarin, decreases the production of coagulation factors, but not interrupts coagulation cascade may not be helpful to decrease hypercoagulability, but increase the risk of bleeding. However, the treatment of cancer-associated embolic stroke is still controversial. This article reviews relevant clinical studies and proposes the applicability of direct oral anticoagulants from the pathophysiological mechanism. 


Phenotypic profile of pulmonary aspergillosis and associated cellular immunity among people living with human immunodeficiency virus in Maiduguri, Nigeria
Idris Abdullahi Nasir, Halima Ali Shuwa, Anthony Uchenna Emeribe, Hafeez Aderinsayo Adekola, Amos Dangana

Tzu Chi Medical Journal 2019 31(3):149-153

Objective: Aspergillus causes many forms of pulmonary infectious diseases ranging from colonization (noninvasive) to invasive aspergillosis. This largely depends on the underlying host&#39;s lung health and immune status. Pulmonary aspergillosis (PA), especially the invasive form, occurs as opportunistic to human immunodeficiency virus (HIV) as a result of cluster of differentiation (CD)4&#43; lymphopenia. The majority of patients with comorbid HIV and aspergillosis go undiagnosed. This study aimed to isolate, identify the etiologies, and determine the prevalence of PA among HIV-infected persons with a productive cough (at least &#60;2 weeks) at the HIV Clinics of the University of Maiduguri Teaching Hospital, Nigeria. Materials and Methods: After ethical approval, three consecutive early morning sputum samples were collected from patients with negative tuberculosis results. The samples were individually inoculated onto Sabouraud dextrose agar supplemented with chloramphenicol and cycloheximide in duplicate for 7 days at 37&#176;C and 25&#176;C, respectively. The fungal isolates were examined morphologically and microscopically and identified using the standard biochemical reagents. CD4&#43; cell counts were performed using flow cytometry. Self-administered questionnaires were used to assess the patients data. All patients were antiretroviral na&#239;ve. Results: The prevalence of PA was 12.7&#37; in these 150 patients. Of the 19 fungal culture-positive individuals, Aspergillus fumigatus accounted for the highest proportion of the isolates (8, 42.1&#37;) followed by Aspergillus niger (5, 26.3&#37;), Aspergillus flavus (4, 21.1&#37;), and Aspergillus terreus (2, 10.5&#37;). Based on the assessment of functionality of cellular immunity, HIV participants who were negative for PA (131/150) had significantly higher mean &#177; standard deviation CD4 T-cell counts (245.65 &#177; 178.32 cells/mL) than those with aspergillosis (126.13 &#177; 105.27 cells/mL) (P &#61; 0.0051). PA was relatively highest among patients with CD4&#43; cell counts &#60;200 cells/mL (12. 34.3&#37;) followed by those with CD4&#43; cell counts between 200 and 350 cells/mL (5, 9.6&#37;) and least among those with CD4&#43; cell counts &#62;350 cells/mL (2, 3.2&#37;). The Chi-square test showed a significant association between the prevalence of PA and the CD4&#43; cell count, age, and gender (P &#60; 0.05) but not with occupation or education level (P &#62; 0.05). Conclusion: The findings from this study indicate that Aspergillus spp. is a significant etiology of acute productive cough in people living with HIV and this is related to the CD4&#43; cell count of coinfected persons. 


Knowledge about and preventive practices against neonatal tetanus among young Nigerian women
CA Adegbenro, Samuel Anu Olowookere, FO Fehintola, PA Adegbenro, OT Orioke

Tzu Chi Medical Journal 2019 31(3):154-157

Objective: The objective of this study was carried out to determine the knowledge about and preventive practices against neonatal tetanus (NNT) in young women of reproductive age. Materials and Methods: Descriptive cross-sectional study design of 380 randomly selected consenting young women of child-bearing age at a Nigerian tertiary educational institution. They completed a semi-structured questionnaire on knowledge about and risk factors for NNT, willingness to receive the vaccine, and uptake of tetanus toxoid vaccine. Results: The mean age (standard deviation) of the women was 22.4 (4.6) years ranging from 15 to 30 years. The majority (64.5&#37;) had poor knowledge of the causes of and risk factors for NNT with only 31&#37; knowing that immunizing women against tetanus prevents NNT. Most of the women (58&#37;) were unwilling to receive tetanus immunization. A total of 15.5&#37; had received tetanus toxoid, but only 0.5&#37; had completed the required dosage. A higher proportion of respondents with good knowledge about tetanus had tetanus toxoid immunization (28.1&#37; vs. 8.6&#37;; P &#60; 0.0001). Conclusion: Knowledge about NNT, willingness to receive the vaccine, and uptake of tetanus toxoid were unacceptably poor among respondents. There is a need for continuous education targeting young women on the link between the tetanus immunization status of women and the occurrence of NNT. 


Comparison of intramuscular methylergometrine, rectal misoprostol, and low-dose intravenous oxytocin in active management of the third stage of labor
Ruchi Jain, Sudesh Agrawal, Kamala Verma, Aastha Jain, Mayank Baid

Tzu Chi Medical Journal 2019 31(3):158-162

Objective: Active management of the third stage of labor (AMTSL) is a critical intervention for the prevention of postpartum hemorrhage (PPH), which is still the most common cause of maternal morbidity and mortality worldwide. The objective of the study is to compare the effect of intramuscular methylergometrine, rectal misoprostol, and low-dose intravenous oxytocin in the AMTSL in terms of amount of blood loss and duration of the third stage of labor, cost-effectiveness, and side effect profile. Materials and Methods: Seventy-five pregnant patients admitted in the maternity ward for vaginal delivery from February 2017 to February 2018 received either intramuscular methylergometrine (0.2 mg) or rectal misoprostol (400 mcg) or low-dose intravenous oxytocin (5 units oxytocin in 100 mL normal saline) for AMTSL. Data were recorded in three groups: Group A (methylergometrine), Group B (misoprostol), and Group C (oxytocin) consisting of 25 cases each. Results: Mean blood loss was found to be least in methylergometrine group (246.87 &#177; 65.44 mL) as compared to misoprostol (346.13 &#177; 58.35 mL) and oxytocin (334.5 &#177; 69.20 mL) (P &#61; 0.000) Mean duration of the third stage of labor was also least in methylergometrine group (6.21 &#177; 1.58 min) (P &#61; 0.0008). Conclusion: Although methylergometrine was found to have higher incidence of side effects such as nausea, vomiting, headache, and raised blood pressure, it was found to be the most effective drug for minimizing blood loss in the third stage of labor. In remote places where healthcare facilities are limited and drugs cannot be administered by parenteral route, rectal misoprostol remains an alternative. 


Optimal imaging time for Tc-99m phytate lymphoscintigraphy for sentinel lymph node mapping in patients with breast cancer
Ching-Chun Ho, Yu-Hung Chen, Shu-Hsin Liu, Hwa-Tsung Chen, Ming-Che Lee

Tzu Chi Medical Journal 2019 31(3):163-168

Objectives: Sentinel lymph node (SLN) sampling has become a standard practice in managing early-stage breast cancer. Lymphoscintigraphy is one of the major methods used. The radioactive tracer used in Taiwan is Tc-99m phytate. However, this agent is not commonly used around the world and the optimal imaging time has not been studied. Thus, we investigated the optimal imaging time of Tc-99m phytate lymphoscintigraphy for SLN mapping in patients with breast cancer. Materials and Methods: We retrospectively reviewed SLN Tc-99m phytate lymphoscintigraphies in 135 patients with breast cancer between August 2013 and November 2017. The time for the first SLN to be visualized after radiotracer injection was recorded to determine the optimal imaging time. If no SLN was identified on imaging, the scan was continued to 60 min. We also recorded the presurgical technical and clinical factors to analyze the risk factors for nonvisualization of SLN. Each patient&#39;s postoperative axillary lymph node status was also recorded. Results: Axillary SLNs were identified on imaging in 94.8&#37; of the patients. All first SLNs presented within 30 min. In 6 of 7 patients with negative imaging, SLNs were identified during surgery using either blue dye or a hand-held gamma probe. Nonvisualization of SLNs on lymphoscintigraphy was significantly associated with a lower injection dose (1.0 mCi vs. 2.0 mCi), 4-injection protocol (compared to 2-injection), and injection around an outer upper quadrant tumor. In addition, patients with axillary lymph node metastasis had a higher percentage of SLN image mapping failure, with a marginally significant difference. Conclusion: Based on our study, 30 min after Tc-99m phytate injection is the optimal time for lymphoscintigraphy and delayed imaging beyond 30 min is not necessary. In addition, a lower injection dose, the 4-injection method, and an injection near the outer upper quadrant tumor should be avoided to minimize nonvisualization of SLNs.


The role of tea and coffee in the development of gastroesophageal reflux disease
Tao-Yang Wei, Pang-Hsin Hsueh, Shu-Hui Wen, Chien-Lin Chen, Chia-Chi Wang

Tzu Chi Medical Journal 2019 31(3):169-176

Objective: The incidence of gastroesophageal reflux disease (GERD) is increasing, and the disease has a close association with dietary habits. This study aims to investigate the role of tea and coffee drinking in the development of GERD. Materials and Methods: This study prospectively enrolled individuals who underwent an upper gastrointestinal endoscopy during a health checkup. Each participant completed the reflux disease questionnaire (RDQ). Coffee or tea drinking was defined as drinking the beverage at least 4 days/week for 3 months. Heavy coffee or tea consumption was defined as drinking at least two cups every day. Results: A total of 1837 participants (970 men; age 51.57 &#177; 10.21 years), who had data on clinical characteristics and consumption of coffee and tea with or without additives such as milk or sugar were included for final analysis. Among them, 467 (25.4&#37;) were diagnosed as having symptomatic GERD based on the RDQ score, and 427 (23.2&#37;) had erosive esophagitis (EE) on endoscopy. Drinking coffee or tea was not associated with reflux symptoms or EE in univariate and multivariate analyses. In contrast, drinking coffee with milk was associated with reflux symptoms and drinking &#8220;tea and coffee&#8221; was associated with EE in univariate analysis. However, these associations became insignificant after multivariate analysis. Conclusion: Drinking coffee or tea and adding milk or sugar was not associated with reflux symptoms or EE. 


Ischemic stroke following neck dissection in the elderly
Chuan-Yi Kuo, Yi-Ting Chen, Cheuk-Kwan Sun, Kuo-Chuan Hung

Tzu Chi Medical Journal 2019 31(3):177-181

Objective: Despite the known association of perioperative stroke with perioperative mortality, the prevalence of stroke following neck dissection in elderly patients remains unclear. This study compared the incidence of neck dissection-associated perioperative stroke in elderly and younger patients. Materials and Methods: Totally, 1057 patients receiving neck dissection for head and neck cancers between June 2012 and July 2016 were reviewed at a single center. The patients were divided into elderly (age &#8805;65 years, n &#61; 177) and younger (age &#60;65 years, n &#61; 880) groups (mean age: 72.3 &#177; 6.1 and 53.3 &#177; 7.6, respectively). Patient, anthropometric, and clinical characteristics including diagnoses, comorbidities, length of hospitalization, and incidence of perioperative stroke were compared. Results: Younger patients were more likely to be male (P &#61; 0.001) and to have received radiotherapy (P &#61; 0.013). The prevalence of predisposing factors was higher in the elderly, including history of cerebral vascular accident (P &#61; 0.002), hypertension (P &#60; 0.001), diabetes (P &#60; 0.001), and coronary artery disease (P &#60; 0.001). Elderly patients also had longer hospitalizations (P &#60; 0.001) for which previous radiotherapy was identified as a risk factor (adjusted odds ratio &#61; 3.79, P &#61; 0.0078). Postoperative ischemic stroke was diagnosed in two elderly patients (1.1&#37;), whereas no ischemic strokes occurred in the younger group (P &#61; 0.028). The overall incidence of perioperative stroke was 0.19&#37;. Conclusion: The incidence of perioperative stroke was higher in the elderly than in the younger group. Furthermore, the prevalence of ischemic stroke in elderly patients associated with neck dissection was higher than that previously reported in the aged population after general head and neck operations, highlighting an increased risk of stroke in elderly patients receiving extensive neck surgery. 


Utilization of a central venous catheter insertion care bundle in Taiwan: A cross-sectional analysis of the National Health Insurance Research Database
Hui-Chun Chung, Lih-Shinn Wang, Jung-Lun Wu, Tsung-Cheng Hsieh

Tzu Chi Medical Journal 2019 31(3):182-187

Objectives: The objectives of this study are to explore medical care utilization associated with promoting the central venous catheter (CVC) care bundle plan using Taiwan&#39;s National Health Insurance Research Database (NHIRD). Materials and Methods: We performed a cross-sectional, secondary analysis of the data from patients who were admitted to a medical center for the first time between July 1, 2010, and June 30, 2012, in the NHIRD. The control group was patients who were admitted at nine medical center hospitals that participated in the pilot plan, and the study group was patients who were admitted at other ten medical center hospitals that did not participate in the pilot plan, and the differences between groups were analyzed. Results: After implementing the CVC care bundle, the average hospital stay decreased significantly (18.43 &#177; 12.96 vs. 15.49 &#177; 10.16, P &#60; 0.05). In addition, the study group patients were clinically less likely to require antibiotics than the control group (odds ratio &#61; 0.33, 95&#37; confidence interval [CI] &#61; [0.07, 1.71] vs. 0.62, 95&#37; CI &#61; [0.40, 0.96], P &#61; 3768), and their medical expenses were lower (220, 618 &#177; 226, 419 vs. 208, 079 &#177; 193, 610, P &#62; 05). Furthermore, the incidence rate of CVC-associated sepsis decreased from 12.59&#37; to 5.66&#37;. Conclusions: By implementing the CVC care bundle in clinical practice in accordance with national policies, medical utilization decreased, thereby considerably improving medical resource usage. These results confirmed that implementing the CVC care bundle possibly decreased medical utilization in clinical practice. 


An objective structured teaching exercise for faculty training and assessment of teaching ability in interprofessional collaborative practice and education
Hsiu-Chen Yeh, Sin-Yi Huang, Tsung-Ying Chen, Ming-Chen Hsieh

Tzu Chi Medical Journal 2019 31(3):188-191

Objective: Improving clinical teachers&#39; ability to teach interprofessional collaborative practice warrants development in current faculty training programs; in particular, current education training emphasizes experiential learning and multiple teaching strategies. The purpose of this study was to establish a teaching model to apply interdisciplinary collaborative care and to improve clinical teachers&#39; execution of interprofessional practices. Materials and Methods: Health-care faculty members were studied; this study assessed a teacher education curriculum for interprofessional education (IPE) and applied an objective structured teaching exercise (OSTE) to evaluate IPE execution by clinical teachers. Results: The OSTE improved clinical teachers&#39; IPE execution, verifying the necessity for multistrategy teaching in faculty training programs. Conclusions: This study provides different types of interprofessional faculty training and assessments. Development of an OSTE requires long-term planning, and IPE should also be incorporated into formal programs. 


Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Minimal Access Surgery

The unwanted third wheel in the Calot's triangle: Incidence and surgical significance of caterpillar hump of right hepatic artery with a systematic review of the literature
Luigi Marano, Alberto Bartoli, Karol Polom, Raffaele Bellochi, Alessandro Spaziani, Giampaolo Castagnoli

Journal of Minimal Access Surgery 2019 15(3):185-191

Background: Caterpillar hump of the right hepatic artery is a rare variation increasing the risk of vascular and biliary injuries during hepatobiliary surgery. The aim of this study is to record the cases of the right hepatic artery forming caterpillar hump in a cohort of patients underwent laparoscopic cholecystectomy and to report a review of the literature systematically conducted. Methods: We reviewed clinical and surgical video data of 230 patients with symptomatic cholelithiasis treated with laparoscopic cholecystectomy between January 2016 and August 2017. A systematic literature search in PubMed, Medline, Cochrane and Ovid databases until 30th June 2017 was also performed in accordance with the PRISMA statement. Results: Our institutional data indicated that 1.3&#37; of 230 patients presented caterpillar hump right hepatic artery. The systematic review included 16 studies reporting data from a total of 498 human cadavers and 579 patients submitted to cholecystectomy. The overall proportion of surgical patients with the caterpillar hump right hepatic artery was 6.9&#37;. Conclusions: Variations of the cystic artery are not just an anatomical dissertation, assuming a very crucial role in surgical strategies to avoid uncontrolled vascular lesions. A meticulous knowledge of the hepatobiliary triangle in association with all elements of &#39;Culture of Safety in Cholecystectomy&#39; is mandatory for surgeons facing more than two structures within Calot&#39;s triangle.


Clip-stone and T clip-sinus: A clinical analysis of six cases on migration of clips and literature review from 1997 to 2017
Liwei Pang, Jindong Yuan, Yan Zhang, Yuwen Wang, Jing Kong

Journal of Minimal Access Surgery 2019 15(3):192-197

Introduction: With the development of laparoscopic skills, the laparoscopic common bile duct exploration (LCBDE) and laparoscopic cholecystectomy (LC) has become the standard surgical procedure for choledocholithiasis. We usually use Hem-o-lok clips to control cystic duct and vessels, which is safe on most occasions and has few perioperative complications such as major bleeding, wound infection, bile leakage, and biliary and bowel injury. However, a rare complication of post-cholecystectomy clip migration (PCCM) increases year by year due to the advancement and development of LC, CBD exploration as well as the wide use of surgical ligation clips. Materials and Methods: Six patients whose clips are found dropping into CBD or forming T-tube sinus after laparoscopic surgery in our department. Results: Six patients whose clips are found dropping into CBD (clip-stone) (3/6) or forming T-tube sinus (T clip-sinus) (3/6) after LCBDE or LC. Conclusions: PCCM is a rare but severe complication of LCBDE. A pre-operative understanding of bile duct anatomy, the use of the minimum number of clips and the harmonic scalpel during the surgeries is necessary. Considering clip-stone or clip-sinus in the differential diagnosis of patients with biliary colics or cholangitis after LCBDE even years after surgery, the detailed medical history and pre-operative examination are inevitable, especially for these patients who had undergone LCBDE.


Extended totally extraperitoneal repair (eTEP) for ventral hernias: Short-term results from a single centre
Sarfaraz Jalil Baig, Pallawi Priya

Journal of Minimal Access Surgery 2019 15(3):198-203

Introduction: There has been a surge of innovative procedures in the field of abdominal wall hernias. Works of pioneers such as Dr. Yuri Novitsky, Dr. Jorge Daes and Dr. Igor Belyansky have started a new era in the field of hernia surgery. Conventional and popular surgeries for ventral hernias are open onlay mesh hernioplasty, open retromuscular mesh hernioplasty (Rives-Stoppa procedure) and laparoscopic intraperitoneal mesh hernioplasty. Evidence seems to suggest that retromuscular mesh hernioplasty has advantages over other procedures regarding recurrence and surgical site occurrences. An alternative strategy has been developed for this setting where a mesh is placed in retromuscular space by minimal access technique of the extended Totally Extraperitoneal approach (eTEP). Methods: We have retrospectively analysed the data of 21 patients who underwent an eTEP procedure with a minimum follow-up of 2 months. Their data were analysed for operative details, intra-operative and post-operative complications. Results: For a total of 21 patients, we have recorded a total of two surgical site occurrences (1 seroma and 1 linea alba dehiscence) and one recurrence. One patient had chronic pain. There was no surgical site infection. Conclusion: Judging from our short-term results, we suggest that the eTEP technique can be adapted in centres with advanced laparoscopic skills with the careful patient selection.


Initial experience with minimally invasive extended pancreatectomies for locally advanced pancreatic malignancies: Report of six cases
Tze-Yi Low, Brian K. P Goh

Journal of Minimal Access Surgery 2019 15(3):204-209

Background: Recently, there have been several reports on minimally-invasive surgery for extended pancreatectomy (MIEP) in the literature. However, to date, only a limited number of studies reporting on the outcomes of MIEP have been published. In the present study, we report our initial experience with MIEP defined according to the latest the International Study Group for Pancreatic Surgery (ISPGS) guidelines. Methods: Over a 14-month period, a total of 6 consecutive MIEP performed by a single surgeon at a tertiary institution were identified from a prospectively maintained surgical database. EP was defined as per the 2014 ISPGS consensus. Hybrid pancreatoduodenectomy (PD) was defined as when the entire resection was completed through minimally-invasive surgery, and the reconstruction was performed open through a mini-laparotomy incision. Results: Six cases were performed including 2 robotic extended subtotal pancreatosplenectomies with gastric resection, 1 laparoscopic-assisted (hybrid) extended PD with superior mesenteric vein wedge resection, 2 robotic-assisted (hybrid) PD with portal vein resection (1 interposition Polytetrafluoroethylene graft reconstruction and 1 wedge resection) and 1 totally robotic PD with wedge resection of portal vein. Median estimated blood loss was 400 (250&#8211;1500) ml and median operative time was 713 (400-930) min. Median post-operative stay was 9 (6&#8211;36) days. There was 1 major morbidity (Grade 3b) in a patient who developed early post-operative intestinal obstruction secondary to port site herniation necessitating repeat laparoscopic surgery. There were no open conversions and no in-hospital mortalities. Conclusion: Based on our initial experience, MIEP although technically challenging and associated with long operative times, is feasible and safe in highly selected cases.


Per-operative modified rigid cholangioscopy for removal of intrahepatic stones associated with choledochal cyst in children
Vikesh Agrawal, Himanshu Acharya, Arjun Saxena, Dhananjaya Sharma

Journal of Minimal Access Surgery 2019 15(3):210-213

Introduction: Choledochal cyst (CDC) is often associated with intrahepatic stones (IHSs) in children which necessitate their removal during excision. The endoscopic equipment needed for their clearance such as paediatric flexible cholangioscope and other advanced modalities are not freely available in resource-poor setups. We describe per-operative modified rigid cholangioscopy using rigid paediatric cystoscope for stone removal during open CDC excision. Methods: All children with CDC presenting with IHSs between January 2015 and December 2017 were included in the present study. IHSs were diagnosed by ultrasound/magnetic resonance cholangiopancreatography (MRCP). In these patients, after cyst excision by open technique, a 9 Fr paediatric cystoscope with 4 Fr working channel was inserted into the common hepatic duct for visualisation and clearance of stones from (intrahepatic bile ducts). Follow-up was done using liver function tests, ultrasound and MRCP (if needed). Patients underwent three monthly liver function test and ultrasound and if needed MRCP. Results: Six cases of CDC presenting with IHS were managed, and one case with post-R-en-Y IHS was treated with this technique. Rigid paediatric cystoscope with working channel and forceps was used. All cases were successfully managed, and one case was found to have intrahepatic duct stenosis was dilated. Conclusion: Per-operative rigid endoscopy using paediatric cystoscope is an easily available tool in most of the setups for the management of IHS associated with CDC in children.


Surgery strategy of 13 cases to control bleeding from the liver on laparoscopic repeat liver resection for recurrent hepatocellular carcinoma
Shuiping Yu, Tang Bo, Binzong Hou, Jiangfa Li, Xueling Zhou

Journal of Minimal Access Surgery 2019 15(3):214-218

Introduction: Laparoscopic repeat liver resection (LRLR) is a safe and effective treatment in recurrent hepatocellular carcinoma (rHCC) in particular patients. However, there are less reports about surgery strategy of LRLR for rHCC. The aim of this study was to perform a systematic strategy for bleeding of liver to increase the safety and feasibility of LRLR for rHCC. Methods: In this study, a total of 13 cases of LRLR for rHCC, including 8 males and 5 females; aged 28&#8211;72 years, mean age 54 years, who were received at least one laparotomy due to HCC. We employ to block the local blood flow, ligation of the left or right hepatic artery and/or approach of Pringle according to the assessment of the degree of adhesions in the abdominal and the first hepatic portal, the location of the tumour (edge/central). Results: Three cases were less adhesions, nine cases were dense adhesions but 1 case was serious adhesions. Two cases were employed to block the local blood flow, 3 cases were employed to ligation of the left or right hepatic artery and 7 cases were employed to approach of Pringle. Twelve cases were successfully completed by LRLR whereas 1 case was completed by transfer to the open resection, including massive resection in 3 cases (the diameter of resection &#8805;3 cm), small hepatectomy in 10 cases (the diameter of resection &#60;3 cm), no severe perioperative complication. The average operative time was (142 &#177; 34) min, the average intraoperative blood loss was (251 &#177; 92) ml and the average post-operative hospital time was (9 &#177; 3) d. The mean follow-up time was 25 months. Until the last follow-up, 11 cases survived while 2 cases died because of tumour recurrence. Conclusions: It can improve the safety and feasibility of LRLR for rHCC, according to the degree of adhesion of the peritoneal adhesions and the first hepatic portal, then selecting the appropriate technique to control the bleeding of the hepatectomy.


Laparoscopic 'steering wheel' derotation technique for midgut volvulus in children with intestinal malrotation
Vikesh Agrawal, Abhishek Tiwari, Himanshu Acharya, Rajesh Mishra, Dhananjaya Sharma

Journal of Minimal Access Surgery 2019 15(3):219-223

Introduction: Since the first description by William Ladd, the Ladd&#39;s procedure has been the surgery of choice for the correction of malrotation. The laparoscopic Ladd&#39;s procedure is becoming popular with the advent of minimal access surgery and is described in the literature. Various techniques of the Ladd&#39;s procedure have been described but none of them describes the stepwise technique for derotation of volvulus which is the most difficult and confusing part of the surgery. We describe &#39;steering wheel&#39; technique for easy derotation of volvulus associated with malrotation. Method: A total of 62 patients were diagnosed to have an intestinal malrotation between 2010 and 2017. All cases which had complete non-rotation with a midgut volvulus were reviewed. Out of these, 48 patients were operated with open technique and 14 patients were subjected to the laparoscopic correction. Technique: Using three-port technique, stepwise derotation of volvulus is done which simulates the rotation of steering of car at an acute turn and has been described in four simple steps. This technique also stresses the importance of the release of Ladd&#39;s band before derotation. Results: Of 62 patients diagnosed with malrotation, 14 (22.6&#37;) patients underwent the laparoscopic Ladd&#39;s procedure. The mean age was 26 &#43; 8 months, mean weight was 10 &#43; 2 kg and included eight males (57&#37;) and six females (43&#37;). There was only one (7.14&#37;) conversion to open technique, due to a huge dilatation of duodenum causing difficulty in dissection in a patient with malrotation without volvulus. The laparoscopic Ladd&#39;s procedure took an average time of 70 &#177; 15 min. Conclusion: The laparoscopic &#39;steering wheel&#39; derotation technique is easy and provides a stepwise description of the laparoscopic derotation of volvulus associated with malrotation in children.


Laparoscopic parastomal hernia repair: A modified technique of mesh placement in Sugarbaker procedure
Sameer Rege, Amiteshwar Singh, Ajinkya Rewatkar, Janesh Murugan, Richard Menezes, Shrinivas Surpam, Roshan Chiranjeev

Journal of Minimal Access Surgery 2019 15(3):224-228

Introduction: Conventional surgery for parastomal hernia entails primary suture repair or stoma relocation. Laparoscopic surgery has advantages of less pain, faster post-operative recovery and better cosmesis. While the Sugarbaker technique has been valued for least recurrences, however, it exposes the stomal loop to the parietal surface of the mesh exposing it to complications. We report a modification of mesh placement after primary defect repair to improvise the safety of meshplasty and to minimise mesh erosions into the stomal loop of bowel. Patients and Methods: Patients with permanent stoma presenting with a parastomal bulge leading to difficulty with stoma care or abdominal distention or pain were included in the study. A pre-operative computed tomography scan was performed in all patients to rule out any recurrence of primary pathology for which stoma was created and to study the abdominal musculature and defects. Results: Of 14 patients, 12 patients had end-sigmoid stoma, one had end ileostomy following surgery for ulcerative colitis and one had urinary conduit. The size of the defect varied from 4.5 cm to 6 cm in diameter, and the average duration of surgery was 125 min. Pain assessed on VAS score was higher in the first 12 h, and all were started on orals on the next day, and average hospital stay was 4.2 days. The longest follow-up of 7 years and shortest of 15 months did not reveal any complications as recurrence, seroma, mesh infections or erosions into the stoma. Conclusion: Modified placement of composite mesh is safe and helps in minimising mesh-related complications of the Sugarbaker technique for parastomal hernias.


A prospective study of gastro-oesophageal reflux disease symptoms and quality of life 1-year post-laparoscopic sleeve gastrectomy
Andrew G.N. Robertson, Andrew J Cameron, Brian Joyce, Phil Le Page, Bruce Tulloh, Andrew C de Beaux, Peter J Lamb

Journal of Minimal Access Surgery 2019 15(3):229-233

Introduction: There are concerns that laparoscopic sleeve gastrectomy (LSG) can cause severe gastro-oesophageal reflux disease (GORD). The aim of this study was to assess GORD symptoms and quality of life following LSG. Methods: A prospective study of patients undergoing LSG (2014&#8211;2016) was performed with follow-up by DeMeester Reflux/Regurgitation Score, Bariatric Quality of Life Index (BQLI) and Bariatric Analysis and Reporting Outcome System (BAROS) Score pre-operatively, 6 months and 1-year post-operatively. Results: Twenty-two patients were studied. Mean modified DeMeester Reflux/Regurgitation Score improved from 2.25 (&#177;0.67) pre-operatively to 0.81 (&#177;0.25) at 12 months (P &#61; 0.04). At 12 months, two patients had symptomatic reflux, but overall satisfaction score was unaffected. Mean BQLI Score underwent a non-significant improvement at 12 months. BAROS Score showed all patients to have excellent (n &#61; 19) or very good (n &#61; 3) results (12 months). Conclusion: GORD symptoms improve for most patients&#39; 1-year post-operatively. A small proportion of patients will develop troublesome GORD, but overall satisfaction remains high. 


Robotic-assisted minimally invasive oesophagectomy for cancer: An initial experience
Chinnusamy Palanivelu, Sumanta Dey, Sandeep Sabnis, Raghavendra Gupta, Bharath Cumar, Saravana Kumar, Ramesh Natarajan, Parthasarathi Ramakrishnan

Journal of Minimal Access Surgery 2019 15(3):234-241

Background: The morbidity related to radical oesophagectomy can be reduced by adopting minimally invasive techniques. Over 250 thoraco-laparoscopic oesophagectomy (TLE) was done in our centre over the last 15 years, before adopting robotic surgery as the latest innovation in the field of minimally invasive surgery. Here, we share our initial experience of robotic-assisted minimally invasive oesophagectomy (RAMIE) for carcinoma oesophagus. Methods: A prospective observational study conducted from February to December 2017. A total of 15 patients underwent RAMIE in this period. Data regarding demography, clinical characteristics, investigations, operating techniques, and post-operative outcome were collected in detail. Results: There were 10 (66.7&#37;) male patients and the median age of all patients was 62.9 (range 36&#8211;78) years. The median body mass index was 24.4 (range 15&#8211;32.8) kg/m2. Twelve (80.0&#37;) patients had squamous cell carcinoma (SCC) of the oesophagus and 3 (20&#37;) patients had adenocarcinoma (AC). Five (33.3&#37;) patients received neoadjuvant therapy. All 15 patients underwent RAMIE. Patients with SCC underwent McKeown&#39;s procedure, and those with AC underwent Ivor Lewis procedure. Extended two-field lymphadenectomy (including total mediastinal lymphadenectomy) was done for all the patients. The median operating time was 558 (range 390&#8211;690) min and median blood loss was 145 (range 90&#8211;230) ml. There were no intra-operative adverse events, and none of them required conversion to open or total thoracolaparoscopic procedure. The most common post-operative complications were recurrent laryngeal nerve paresis (3 patients, 20.0&#37;) and pneumonia (2 patients, 13.3&#37;). The median hospital stay was 9 (range 7&#8211;33) days. In total, 9 (60&#37;) patients required adjuvant treatment. Conclusion: Adequate experience in TLE can help minimally invasive surgeons in easy adoption of RAMIE with satisfactory outcome.


Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Clinical Cancer Investigation

Response assessment of gefitinib therapy in the epidermal growth factor receptor- mutant advanced adenocarcinoma lung at a tertiary care center in North India
Anubhuti Singh, Anand Srivastava, Abhishek Verma, Rajiv Garg

Clinical Cancer Investigation Journal 2019 8(2):41-46

Context: Oral tyrosine kinase inhibitors (TKIs) have been proven to improve response rates (RRs) and progression-free survival in a chemo-na&#239;ve setting in the epidermal growth factor receptor (EGFR)-mutant advanced lung adenocarcinoma patients in studies conducted in Western countries. Similar data from India are currently sparse. Aims: The aim is to study the epidemiological, clinical, and radiological profile of advanced-stage of lung adenocarcinoma patients harboring an EGFR mutation and to assess the response of TKIs in these patients. Settings and Design: This was a prospective observational study performed at a tertiary care hospital. Materials and Methods: A total of 40 advanced-stage lung adenocarcinoma patients who harbored an EGFR mutation and received an oral TKI (gefitinib) were included in the study and response was evaluated using the Response Evaluation Criteria for Solid Tumors. Statistical Analysis Used: Qualitative variables were compared using the Chi-square test/Fisher&#39;s exact test as appropriate. Results: A total of 30 (75&#37;) patients had an exon 19 mutation and 3 (7.5&#37;) patients had an exon 21 mutation. The overall RR to gefitinib was 57.5&#37;. Eleven (27.5&#37;) patients had partial response, 12 (30&#37;) patients had stable disease (SD), and 6 (15&#37;) patients had progressive disease. The RR was more favorable among females, rural residents, nonsmokers, patients having good performance score, and stage III disease. Conclusions: The overall RR to gefitinib was comparable to those reported in western studies but lower than those reported in Asian studies at our center. 


Surgical margins and nodal metastasis are prognostic factors in oral squamous cell carcinoma: A meta-analysis
Mohammad Akheel, Rinku K George, Amit Jain, Qutubuddin Chahwala, Ashmi Wadhwania

Clinical Cancer Investigation Journal 2019 8(2):47-51

Background: To find out whether surgical margins and nodal metastasis are prognostic factors in oral squamous cell carcinoma (OSCC). Materials and Methods: PubMed search was done to look for studies done on surgical margins and nodal metastasis of OSCC from 2008 to 2018. Results: Fixed effects meta-analysis showed a pooled estimate absolute risk reduction of &#8722;3&#37; (95&#37; confidence interval [CI] [&#8722;8, 2.5&#37;]). P &#61;0.2819 from the fixed margin model shows no statistically significant difference between close margins with cases of deaths due to recurrence or metastasis. The pooled odds ratio was 0.87 (95&#37; CI 0.63&#8211;1.99, P &#61; 0.3928) for the comparison between clear and closed margins for estimating the odds. It should be noted that the mean unweighted local recurrence rate for margins 5 mm or greater was 4.9&#37; with 95&#37; CI as &#8722;10.7&#37;, 0.8&#37;. Conclusion: The study shows that close surgical margins with nodal metastasis have a poor prognosis in OSCC; however, no statistical significance was seen in this meta-analysis. 


Impact of body mass index on breast cancer subtypes in Iranian women
Hamid Ahmadi, Bita Eslami, Sadaf Alipour, Adel Yazdankhahkenary, Ramesh Omranipour

Clinical Cancer Investigation Journal 2019 8(2):52-56

Background: The incidence of obesity as one of the risk factors of breast cancer (BC) is increasing dramatically. Our objective was to evaluate the association between body mass index (BMI) and three subtypes of BC in Iranian women. Materials and Methods: In this retrospective study, BC patients&#39; information was recorded by referring to their medical records in the Cancer Institute of Imam Khomeini Hospital, Iran, from 2015 to 2017. The data of 374 patients were entered into the study, and tumor data were classified into three groups by molecular markers (human epidermal growth factor receptor 2 [HER2] enriched, triple negative, and luminal). Results: Luminal subtype comprised the majority (71.1&#37;) of all diagnosed BC patients. The proportion of obese women was higher in triple-negative group (35.3&#37;), although the differences between three subtypes of BC were not statistically significant (P &#61; 0.30). Multivariate logistic among cases only, considering luminal as the comparison group, indicated a positive association between age of menarche and HER2-enriched subtype (odds ratio [OR] &#61; 1.18, 95&#37; confidence interval [CI]: 0.99&#8211;1.41, P &#61; 0.07) and also suggested a reverse association between age at time of diagnosis and triple-negative subtype (OR &#61; 0.97, 95&#37; CI: 0.95&#8211;1, P &#61; 0.09) with borderline significance. Conclusion: We did not find any statistically significant differences in BMI between three subtypes of BC. It seems that there is a correlation between triple-negative subtypes of BC in Iranian population and obesity. However, further studies with larger sample size are needed. 


An evaluation of special AT-rich sequence-binding protein 2 expression in primary epithelial tumors and metastatic tumors of the ovary
Esra Oz, Zehra Bozdag, Neslihan Bayramoglu Tepe, Zeynep Bayramoglu, Omer Faruk Dizibuyuk, Metin Karakok

Clinical Cancer Investigation Journal 2019 8(2):57-63

Background: Ovarian cancer is the second most common gynecologic cancer in women. Differential diagnosis between primary and metastatic neoplasms can be problematic in some cases. The special AT-rich sequence-binding protein 2 (SATB2) is a nuclear matrix-associated protein that is important for growth and development. SATB2 has been shown to be a sensitive and highly specific marker for colorectal carcinomas (CRCs). SATB2 expression has also been reported in lung, breast, pancreas, renal, laryngeal, esophageal carcinomas and bone cancers. In this study, we aimed to evaluate SATB2 expression in primary epithelial and metastatic ovarian tumors and determine its significance in differentiating between subtypes. Material and Methods: The study group comprised 148 cases of primary epithelial tumor and 29 cases of metastatic ovarian tumor. Immunohistochemical analysis was performed by applying SATB2 on paraffin blocks. Results: SATB2 expression was identified in 54.5&#37; of mucinous carcinomas, 51.7&#37; of endometrioid carcinomas, 18.2&#37; of high-grade serous carcinomas, 17.9&#37; of borderline mucinous tumors, 6.7&#37; of borderline serous tumors, and 51.7&#37; of metastatic ovarian tumors. SATB2 expression did not show specificity for any of the subgroups. Metastatic ovarian tumors originating from the colon, breast, upper gastrointestinal tract, and appendix also showed SATB2 expression at different rates. All of the metastatic CRCs showed SATB2 positivity. Conclusion: It must be considered that primary carcinomas and metastatic carcinomas may manifest varying levels of SATB2 expression with different intensity and extensiveness. Extensive and strong SATB2 expression indicates metastatic colon carcinoma, consistent with the literature. Further comprehensive studies are needed in order to investigate SATB2 specificity for different subtypes. 


A study of clinicopathologic features of thyroid cancer in Western Iran: A 9-year experience
Babak Izadi, Somayeh Jalilian, Mazaher Ramezani, Masoud Sadeghi, Sedigheh Khazaei

Clinical Cancer Investigation Journal 2019 8(2):64-69

Introduction: Thyroid cancer is reported as the most rapidly increasing and third-most common cancer among females. This study aimed to evaluate the data related to thyroid cancer in Kermanshah, Iran, for the first time. Materials and Methods: The data of thyroid cancers were obtained between March 2008 and March 2017. Tumors were classified into four groups: papillary, follicular, medullary, and anaplastic; age was divided into two groups (&#60;45 years and &#8805;45 years); and tumor size was divided into three groups (&#8804;2, 2&#8211;4, and &#62;4 cm) according to the National Comprehensive Cancer Network guidelines for patients: Thyroid cancer, version 1, 2017. Results: A total of 296 thyroid cancer patients with the mean age of 41.1 years, 75&#37; of whom were female, were studied. Most patients (89&#37;) had papillary thyroid cancer. Of all patients, 8.8&#37;, 21.3&#37;, 20.6&#37;, 27&#37;, 5.7&#37;, and 16.9&#37; of patients had extrathyroidal invasion, lymph node metastasis, capsular invasion, Hashimoto&#39;s thyroiditis, distant metastasis, and goiter, respectively. With regard to the stage, 82.4&#37; of patients had Stage I. There were significant differences between the two genders in the mean age and Hashimoto&#39;s thyroiditis. There were significant differences between the two age groups in sex and Hashimoto&#39;s thyroiditis. In addition, there were significant differences between tumor size group and laterality and vascular invasion. Conclusions: The mean age and female/male ratio in this study were similar to those of other areas of Iran. Papillary thyroid carcinoma is the most common kind of thyroid cancer in Iran. In addition, more attention should be paid to the role of Hashimoto&#39;s thyroiditis in Iranian patients with thyroid cancer in the future. 


Metaplastic chondroid breast carcinoma: A diagnostic challenge
Milind Anil Bhatkule

Clinical Cancer Investigation Journal 2019 8(2):70-72

Metaplastic carcinoma of the breast is a rare entity. Extensive chondroid differentiation is even rarer in metaplastic breast carcinoma (MBC). Here, we report a case of metaplastic chondroid carcinoma of the breast with very few areas showing usual ductal carcinoma and pseudosarcomatous areas. The tumor was characterized by an abundant chondromyxoid matrix. The definitive areas of classic invasive ductal carcinoma were very few. The peripheral portion of the tumor showed increased cellularity with pleomorphism and invasive growth pattern with giant tumor cells. This case is presented for its rarity and also of a diagnostic challenge, especially if the tumor is composed mainly of sarcomatous elements with extensive chondroid differentiation. Standard chemotherapy regimens are ineffective against MBC. 


Superficial extraskeletal ewing's sarcoma of forefoot with inguinal lymph node metastasis and lung metastasis: A rare case
Poorva Vias, Shabnum Thakur, Rajeev K Seam, Vikas Fotedar, Ashish Saklani

Clinical Cancer Investigation Journal 2019 8(2):73-75

Ewing&#39;s sarcoma is the 2nd most common paediatric bone tumour but can also be seen in extraskeletal sites. Superficial extraskeletal ES is a rare entity and is rarely seen in foot. Majority of these patients are females in second decade of life, presenting with small, single mass, mobile, sometimes painful. They usually have a favourable outcome due to infrequent metastasis. 


Priapism in a pediatric chronic myeloid leukaemia patient: Unusual presentation of a rare disease in children
Purnima Thakur, Vishal Verma, Vikas Fotedar, Kalindi Singh

Clinical Cancer Investigation Journal 2019 8(2):76-78

A rare case of chronic myeloid leukemia (CML) presenting with priapism is reported in a pediatric patient. CML accounts for around 15&#37; of hematological malignancies. It is still rarer in the pediatric age group. Investigations revealed hyperleukocytosis due to CML. When conservative management failed, priapism was relieved by shunt procedures and the patient was treated with oral chemotherapy. This case demonstrates the importance of early identification of the underlying cause of priapism, and that the possibility of CML may be kept in mind in pediatric patients too, as it directly influences the management and early diagnosis may preserve sexual function in later life. 


Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480